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      The CXCL12 (SDF-1)/CXCR4 chemokine axis: Oncogenic properties, molecular targeting, and synthetic and natural product CXCR4 inhibitors for cancer therapy

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          Abstract

          Chemokine 12 (CXCL12), also known as stromal cell derived factor-1 (SDF-1) and a member of the CXC chemokine subfamily, is ubiquitously expressed in many tissues and cell types. It interacts specifically with the ligand for the transmembrane G protein-coupled receptors CXCR4 and CXCR7. The CXCL12/CXCR4 axis takes part in a series of physiological, biochemical, and pathological process, such as inflammation and leukocyte trafficking, cancer-induced bone pain, and postsurgical pain, and also is a key factor in the cross-talking between tumor cells and their microenvironment. Aberrant overexpression of CXCR4 is critical for tumor survival, proliferation, angiogenesis, homing and metastasis. In this review, we summarized the role of CXCL12/CXCR4 in cancer, CXCR4 inhibitors under clinical study, and natural product CXCR4 antagonists. In conclusion, the CXCL12/CXCR4 signaling is important for tumor development and targeting the pathway might represent an effective approach to developing novel therapy in cancer treatment.

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          Author and article information

          Journal
          CJNM
          Chinese Journal of Natural Medicines
          Elsevier
          1875-5364
          20 December 2018
          : 16
          : 11
          : 801-810
          Affiliations
          1Center For Drug Evaluation, China Food and Drug Administration, Beijing 100022, China
          2State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China
          Author notes
          *Corresponding author: ZHAO Li, Tel/Fax: 86-25-83271055, E-mail: zhaoli@ 123456cpu.edu.cn

          ΔThese authors contributed equally to this work.

          These authors have no conflict of interest to declare.

          Article
          S1875-5364(18)30122-5
          10.1016/S1875-5364(18)30122-5
          30502762
          Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funding
          Funded by: National Natural Science Foundation of China
          Award ID: 81773774
          Award ID: 81473231
          Award ID: 81673461
          Funded by: Science Foundation for Distinguished Young Scholars of Jiangsu Province
          Award ID: BK20150028
          Funded by: National Science and Technology Major Project
          Award ID: 2017ZX09301014
          Funded by: Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University
          Award ID: SKLNMZZCX201823
          Funded by: Program for Changjiang Scholars and Innovative Research Team in University
          Award ID: IRT1193
          Funded by: Open Project of State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine
          Award ID: TCMQ& E201704
          This work was supported by the National Natural Science Foundation of China (Nos. 81773774, 81473231, and 81673461), Science Foundation for Distinguished Young Scholars of Jiangsu Province (No. BK20150028), the National Science and Technology Major Project (No. 2017ZX09301014), the Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (No. SKLNMZZCX201823), Program for Changjiang Scholars and Innovative Research Team in University (No. IRT1193), and the Open Project of State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine (No. TCMQ& E201704).
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